超级增强子在肿瘤研究中的进展

Research progress of super enhancer in cancer

超级增强子是由多个相邻近的普通增强子组成的、驱动调控细胞身份基因表达的一个大簇,该区域富集高密度的转录因子、辅因子及增强子相关表观修饰。超级增强子所驱动的异常转录基因对维持肿瘤细胞特性至关重要。肿瘤细胞通过组装自身超级增强子,显著促进多种癌基因表达,从而增强肿瘤细胞的增殖、侵袭和转移的能力;抑制超级增强子的活性,则显著抑制肿瘤细胞的生长和存活。本文对目前报道的肿瘤细胞中超级增强子的结构特征和功能调控,以及靶向超级增强子药物研发现状进行了总结,旨在为研发新的针对超级增强子为靶点的抗肿瘤药物提供理论基础和借鉴。

Super enhancers(SEs)are composed of clusters of enhancers in close genomic proximity.They constitute a large family of regulatory elements that specify gene expression patterns and cell identity.SE regions consist of unusually strong enrichment of binding sites for transcriptional factors,cofactors,and enhancers associated with epigenetic modifications.SEs play important roles in regulating the aberrant gene expression in tumor cells.Via SEs,cancer cells activate the expression of various oncogenes,and promote cell proliferation,invasion and migration properties.Hence suppression of SEs activities could inhibit the growth and survival of cancer cells.In this review,we summarize the fundamental principles,functions and regulation of super enhancers and therapeutic potential in targeting SEs in cancer cells,thereby introducing and providing new conceptions for development of antineoplastic drugs.